Frontotemporal lobar degeneration (FTLD) with ubiquitin/TDP-43-positive inclusions (FTLD-TDP) and Pick's disease are two major pathological substrates in sporadic FTLD patients. Although identifying these underlying pathologies during the life of the patient is crucial for specific pathology-based treatment in the future, adequate clinical data to infer pathologies are not available. Several recent studies demonstrated that Pick's disease cases tend to present clinically with frontotemporal dementia (FTD) or progressive non-fluent aphasia as the first syndrome, while sporadic FTLD-TDP cases frequently show semantic dementia. Some asymmetric motor disturbances (e.g., pyramidal signs, parkinsonism, and contracture) are frequent in sporadic FTLD-TDP during the course, but rare in Pick's disease. On the other hand, several previous studies have demonstrated that the most frequent first syndrome of FTLD-TDP with progranulin gene (PGRN) mutations is FTD and that neuronal loss in the frontal cortex is more severe than that in the temporal cortex. Therefore, it is plausible that the clinicopathological features of sporadic FTLD-TDP are different from those of Pick's disease and FTLD-TDP with PGRN mutations. Given that in vivo Abeta imaging will soon be put to practical use, clinical data useful for clinical differentiation of pathological subtypes of FTLD besides AD with atypical cerebral atrophy will be essential in the future.